Polymorphism of the fractalkine receptor CX3CR1 and systemic sclerosis-associated pulmonary arterial hypertension.
Polymorphism of the fractalkine receptor CX3CR1 and systemic sclerosis-associated pulmonary arterial hypertension.
复制标题
DOI：
10.1080/17402520500303297
复制
发表时间：
2005-12
影响因子：
--
通讯作者：
Biondi, Maria Luisa
中科院分区：
文献类型：
--
作者：
Marasini, Bianca;Cossutta, Roberta;Selmi, Carlo;Pozzi, Maria Rosa;Gardinali, Marco;Massarotti, Marco;Erario, Maddalena;Battaglioli, Lodovica;Biondi, Maria Luisa
Fractalkine(FKN)及其受体CX3CR1在包括系统性硬化症(SSC)和肺动脉高压(PAH)在内的多种慢性疾病的血管和组织损伤中起重要作用。有趣的是，V249I和T280M基因多态性影响CX3CR1的表达和功能。我们调查了这些多态是否与继发于SSC的PAH相关。应用聚合酶链式反应和测序技术对76例局限性SSc患者和204例正常对照进行CX3CR1基因分型。彩色多普勒超声心动图确定PAH。在SSc患者中，249II纯合子以及249II和280 mM联合存在的频率显著高于对照组(分别为17vs6%，p=0.0034和5vs1%，p=0.0027)。249I和280M等位基因与PAH相关(奇比[OR]2.2，95%可信区间[CI]1.01~4.75，p=0.028和OR7.37，95%CI：2.45~24.60，p=0.0001)。总之，在SSc相关的PAH患者亚组中，249I和280M CX3CR1等位基因频率的增加表明Fractalkine系统在这种疾病的发病机制中发挥了作用。此外，249I等位基因可能与SSc的易感性有关。
Fractalkine (FKN) and its receptor CX3CR1 are critical mediators in the vascular and tissue damage of several chronic diseases, including systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH). Interestingly, the V249I and T280M genetic polymorphisms influence CX3CR1 expression and function. We investigated whether these polymorphisms are associated with PAH secondary to SSc. CX3CR1 genotypes were analyzed by PCR and sequencing in 76 patients with limited SSc and 204 healthy controls. PAH was defined by colorDoppler echocardiography. Homozygosity for 249II as well as the combined presence of 249II and 280MM were significantly more frequent in patients with SSc compared to controls (17 vs 6%, p = 0.0034 and 5 vs 1%, p = 0.0027, respectively). The 249I and 280M alleles were associated with PAH (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.01-4.75, p = 0.028 and OR 7.37, 95%CI: 2.45-24.60, p = 0.0001, respectively). In conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a subgroup of patients with SSc-associated PAH suggest a role for the fractalkine system in the pathogenesis of this condition. Further, the 249I allele might be associated with susceptibility to SSc.